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Updated: May 20, 2026

Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
Published on: September 28, 2022
The bacteriophage HK97 gp15 moron element encodes a novel superinfection exclusion protein
Nichole Cumby1, Aled M Edwards, Alan R Davidson
1Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Abstract:
A phage moron is a DNA element inserted between a pair of genes in one phage genome that are adjacent in other related phage genomes. Phage morons are commonly found within phage genomes, and in a number of cases, they have been shown to mediate phenotypic changes in the bacterial host. The temperate phage HK97 encodes a moron element, gp15, within its tail morphogenesis region that is absent in most closely related phages. We show that gp15 is actively expressed from the HK97 prophage and is responsible for providing the host cell with resistance to infection by phages HK97 and HK75, independent of repressor immunity. To identify the target(s) of this gp15-mediated resistance, we created a hybrid of HK97 and the related phage HK022. This hybrid phage revealed that the tail tube or tape measure proteins likely mediate the susceptibility of HK97 to inhibition by gp15. The N terminus of gp15 is predicted with high probability to contain a single membrane-spanning helix by several transmembrane prediction programs. Consistent with this putative membrane localization, gp15 acts to prevent the entry of phage DNA into the cytoplasm, acting in a manner reminiscent of those of several previously characterized superinfection exclusion proteins. The N terminus of gp15 and its phage homologues bear sequence similarity to YebO proteins, a family of proteins of unknown function found ubiquitously in enterobacteria. The divergence of their C termini suggests that phages have co-opted this bacterial protein and subverted its activity to their advantage.
Insights
Bacteriophage HK97
Area of Science:
- Microbiology
- Virology
- Molecular Biology
Background:
- Phage morons are DNA elements found in phage genomes that can alter bacterial host phenotypes.
- The temperate phage HK97 contains a unique moron element, gp15, in its tail morphogenesis region.
Purpose of the Study:
- To investigate the function of the gp15 moron in phage HK97.
- To determine the mechanism of gp15-mediated resistance to phage infection.
Main Methods:
- Expression analysis of gp15 from the HK97 prophage.
- Construction of a hybrid phage (HK97/HK022) to identify gp15 targets.
- Transmembrane prediction analysis of gp15 protein.
Main Results:
- gp15 confers resistance to phages HK97 and HK75, independent of repressor immunity.
- Hybrid phage studies suggest tail tube or tape measure proteins are involved in gp15 susceptibility.
- gp15's N-terminus has a predicted membrane-spanning helix, inhibiting phage DNA entry.
Conclusions:
- gp15 functions as a superinfection exclusion protein, preventing phage DNA entry.
- gp15 likely evolved from a bacterial YebO protein, co-opted by phages for their advantage.
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